Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.
Cancer Prev Res (Phila). 2022 Aug 1;15(8):543-552. doi: 10.1158/1940-6207.CAPR-21-0552.
Fecal immunochemical tests (FITs) are increasingly used as noninvasive screening tests in colorectal cancer-screening programs. Polygenic risk scores (PRS) are increasingly propagated for risk stratification in colorectal cancer screening. We aimed to assess the potential of combining FIT results and PRS to enhance diagnostic accuracy of detecting advanced neoplasia (AN) compared with using FIT results alone. Of 10,362 participants of screening colonoscopy in Southern Germany who conducted either one of two quantitative FITs, genotyping was done in all participants with AN (colorectal cancer or advanced adenoma) and a random subset of controls. Among 5,306 individuals, a PRS was calculated on the basis of the number of risk alleles in 140 SNPs. Partial areas under the receiver operating characteristics (ROC) curves (pAUCs) were computed for FIT and PRS alone and combined, focusing on a specificity range of 100%-80%. Both FITs showed similar performance characteristics with pAUCs of 0.661 (95% confidence interval (CI), 0.625-0.698; Ridascreen Hemoglobin) and 0.682 (95% CI, 0.661-0.701; FOB Gold) for AN detection. PRS alone reached a pAUC of 0.524 (95% CI, 0.499-0.550) and 0.530 (95% CI, 0.516-0.545), respectively, and its addition to FIT did not improve pAUCs (0.659; 95% CI, 0.622-0.697) and 0.667 (95% CI, 0.650-0.687), respectively. This finding was confirmed by investigating sensitivities at fixed specificities at 85%, 90%, and 95%. Partial AUCs also did not improve when adding the weighted PRS to FIT instead of the unweighted PRS. In summary, the combination with PRS did not improve diagnostic accuracy of FIT-based screening in a large asymptomatic colorectal cancer screening population from South-Western Germany.
In our study, combining polygenic risk score with fecal immunochemical test (FIT) did not improve diagnostic accuracy for advanced colorectal neoplasia detection compared with FIT alone. So far, such a combination cannot be recommended because it would come at extra costs and effort despite no relevant gain in neoplasia detection.
评估将粪便免疫化学检测（FIT）结果与多基因风险评分（PRS）相结合，与单独使用 FIT 结果相比，是否能提高检测高级别腺瘤（AN）的诊断准确性。
在德国南部进行筛查性结肠镜检查的 10362 名参与者中，有 5306 人进行了两种定量 FIT 检测中的一种，所有有 AN（结直肠癌或高级腺瘤）的参与者和随机部分对照组都进行了基因分型。基于 140 个 SNP 中的风险等位基因数量，计算了 PRS。针对 100%-80%的特异性范围，计算了 FIT 和 PRS 单独使用和联合使用的部分接受者操作特征（ROC）曲线下面积（pAUC）。
两种 FIT 检测在检测 AN 方面的表现相似，pAUC 分别为 0.661（95%CI，0.625-0.698；Ridascreen 血红蛋白）和 0.682（95%CI，0.661-0.701；FOB Gold）。PRS 单独使用时，pAUC 分别为 0.524（95%CI，0.499-0.550）和 0.530（95%CI，0.516-0.545），而添加到 FIT 中并没有提高 pAUC（分别为 0.659 和 0.667）。在固定特异性为 85%、90%和 95%时，灵敏度的检测结果也证实了这一发现。当将加权 PRS 添加到 FIT 中而不是未加权 PRS 时，pAUC 也没有改善。
在德国西南部的一个大型无症状结直肠筛查人群中，将 PRS 与 FIT 结合使用并不能提高 FIT 筛查的诊断准确性。到目前为止，由于这种组合不会增加结直肠肿瘤的检测，且需要额外的成本和精力，因此不能推荐这种组合。
